Hydroxy-octahydronaphthalenes



United States Patent C HYDROXY-OCTAHYDRONAPHTHALENES Max Stoll and Max Hinder, Geneva, Switzerland, as-

signors to Firmenich et Cie, Geneva, Switzerland, 21 Swiss company No Drawing. Application January 25, 1957, Serial No. 636,252

15 Claims. (Cl. 260-617) This invention is a continuation-in-part of our copending application Serial No. 422,686 filed April 12, 1954, now abandoned, and relates to new chemical compounds, to new compositions of matter having a new, strong and very interesting scent, andto a process for preparing the said new compounds and compositions of matter.

According to this invention, -dihydroionone (Formula I) is subjected to a ring closure with the aid of a cyclization agent, such as protons (hydrogen ions and substances furnishing hydrogen ions such as acids, BR: and the like) so as to form a bicyclic car-bonium-ion (Formula II). The latter loses again one proton and yields, besides certain quantities of non-alcoholic by-products, a mixture of isomeric unsaturated tertiary, bicyclic alcohols (Forice Density at 4 7 3,5-dinitrobenzoate: M. P. 8283 C.

This product gives allophanates melting, respectively, at

184 C., 183 C., 172 C. and 154 C., and epoxides C13H2202), the principle melting at -56 C.

Further objects of the invention, also, are the new and Refractive index n industrial products comprising a mixture which containv only the two isomeric alcohols of Formulae III and IV, as well as the individual alcohols of Formulae III and IV separated from such mixtures.

If, in the above-mentioned ring closing, a mixture of cc, 5 and 'y isomers of dihydroionone is used as starting mulae III,IV and V). material in place of the pure 7 isomer, substantially CH5 CH3 CH; CH;

. G\ CE: e C\ Cg: on, on on, H on, 06 OH:

[ OH: i0 Hz --OH 0 z CH CH; CH: C 1 OH I II CH; CH: 0H; CH; 0H, 0H,

fii fii' fii cm on on, on, c on, on, (:H CH2 '2 9 7 '2 "9 7' l2 9 7' 3 6 a 6 s *6 OH: C CHa Ci: /0 /o Ha Oil C OH: 4 5 0H 4 5 0H 4 s OH CH CH2 CH2 CH2 OH OH 111 IV v These alcohols may be separated from the crude reaction mixture, for instance, by a treatment with triethylborate. Two of these three isomeric alcohols occur in two stereoisomeric forms according to their two asymmetrical carbon atoms.

The most important of these alcohols is the alcohol of the Formula III, i.

portance of these alcohols is the alcohol of Formula IV, i. e., 1,1,6-trimethyl-6-hydroxy-1,2,3,4,5,6,7,8-octahydronaphthalene.

Both these alcohols of Formulae III and IV have a new and interesting fragrance and are new anduseful compounds for the perfume industry.

The alcohol of Formula V, i. e., 1,1,6-trimethyl-6-hydroxy-l,2,3,4,6,7,8,9-octahydro-naphthalene, only forms in very small quantities at the time of the ring closure mentioned above. Its odor is rather weak, so that its presence either in the mixture. of the other two alcohols of Formulae III and IV, or in one or the other of these alcohols, does not substantially aifect' the odor of these products. This alcohol of Formula V gives two alloe., 1,1,6-trimethyl-6-hydroxyp 1,2,3,5,6,7,8,9-0ctahydro-naphthalene. The second inimonly the 'y-isomer undergoes the. ring-closure. This results in a mixture of oz and eventually B-dihydroionones with 1,1,6-trimethyl-6-hydroxy-1,2,3,5,6,7,8-,9-octahydronaphthalene, 1,1,6 trimethyl 6 hydroxy l,2,3,4,5,6, 7,8-octahydro-naphthalene, and a small quantity of 1,1,6- trimethyl 6 hydroxy 1,2,3,4,6,7,8,9 octahydro naphthalene, from which the alcohols of Formulae III and IV can be easily separated by borat-ization and fractional methyl 6 hydroxy 1,2,3,4,5,6,7,8 octahydro-naph thalene (Formula IV) gives a single allophanate melting at l53154 C. and having the following physical constants: B. P. 60-61 C. under 0.05 mm, Hg; d4 =0;970; n =1.502. v

The present invention also includes a new process for preparing either the aforesaid new chemical compounds or the above new compositions of matter as mixtures. This new process consists in submitting y-dihydroionone, a. mixture of 'y-dihydroionone and at least one of its isomeric dihydroionones, or acid hydrolizable keto derivatives of these dihydroionones to a ring closure with the aid of a cyclizing agent.

The ring-closing to an isocyclic ring of a monocyclic aliphatic compound having a keto group and a semicyclic double bond has never hitherto been described in the literature. A semicyclic double bond is illustrated in Formula I and refers to double bonded carbon atoms in which only one of the double bonded carbon atoms is in a ring structure; One could not even imagine that such cyclization would be possible. On the one hand, as the semicyclic double bond of 'y-dihydroionone has a strong tendency to enter the ring in the presence of protons (hydrogen ions) or hydroxy groups, such ring-closing seemed quite unlikely. On the other hand, it was highly improbable that in the presence of protons the resulting tertiary hydroxy group would be stable enough to avoid the formation of a double bond. However, in spite of these conjectures, the aforesaid ring-closure can be effected by shaking 'y-dihydroionone (an isomeric mixture or acid hydrolizable keto derivative thereof as stated above) with diluted strong aqueous acids or by heating the 'y-dihydroionone with weak proton-producing substances such as water and weak organic acids, such as phthalic acid, salicylic acid, tartaric acid, benzoic acid, citric acid, oxalic acid, etc. Under these conditions only a small amount of the tertiary alcohol loses its hydroxy group and gives a doubly unsaturated hydrocarbon.

Electrophilic substances, such as BFa may effect the cyclization of 'y-dihydroionone, as well as such ordinary acid proton-producing substances.

The new process is especially interesting when applied to a mixture of u,,3,'y-dihydroionones. It then effects the cyclization of the 'y-isomer only, leaving the other isomers mainly unchanged, so that they may either be used for the preparation of the said mixture (see copending application Serial No. 422,685), or remain in admixture with the new alcohols, giving a fine smelling composition of matter.

The new process of the present invention also works with y-dihydroionone in statu nascendi, that it, with its readily hydrolizable keto derivatives, for example, with its acetal, semi-carbazone or other carbonyl compounds which liberate said y-dihydroionone under the acid conditions of the cyclization. The only requirement necessary to make use of these compounds, instead of the free ketone, is that they should easily cleave into the ketone under the aforesaid reaction conditions.

The new products of this invention are very valuable for use as perfumes or as raw materials for blending in the perfume industry.

The following examples show how the invention may be performed:

EXAMPLE 1 10 g. of pure synthetic 'y-dihydroionone (dd =0.9149; n =1.4771) are shaken for 48 hours at about 25 C. with a solution of 20 g. of concentrated H2SO4in 100 ml. Water. The reaction product is extracted with ether, washed with carbonate and water. The ether solution is dried and the solvent distilled off. The remaining prod uct is heated slowly with g. of B (OC2H.=.)3 for a period of one hour. The ethyl alcohol formed is distilled 01f, together with the excess of ethylborate at ordinary pressure. Then the non-reacted part of the reaction product is distilled off at 0.01 mm. Hg. pressure. The oil bath is held at a temperature not over 140 C. The molecular distillation increases the yield. The residue of the dis tillation is saponified with 70 ml. of 10% methanolic KOH in the presence of 10 ml. benzene, for one hour.

4 The solvents are distilled ofl? and the residue extracted with benzene. Finally, the latter is distilled OE and the remaining product rectified.

EXAMPLE 2 77.8 g. of a mixture of 'y and a-dihydroionones, prepared according to the process of copending application Serial No. 422,685 and having the approximate physical constants: B. P. 0.1 mm. Hg 85 C.; (14 :0920; n

Found 1.475; carbonyl content 95%, are shaken for 48 hours with 800 ml. of a 20% solution of sulfuric acid at about 150-30 C. The reaction product is extracted with ether or benzene. About 76 g. of product is obtained having a ketone content of about 38% (measured by oximation). Therefore, the above treatment has cyclized 95 --38= 57% of the ketones. As the a and fi-dihydroionones do not show any ring-closing under the above conditions, the y-dihydroionone content of the raw material was at least 57 77.8=44.5 g. 74 g. of the cyclized product is heated with 80 g. triethylborate. First the temperature is kept at 128 C. It is then gradually raised to 150 C. At the same time, the pressure is lowered from 720 mm. Hg to 15 mm. Hg, and finally 0.1 mm. Hg. After the ethanol is distilled off, 41 g. distils between 128100 C. under a pressure below 18 mm. Hg and 0.1 mm. Hg. These 41 g. contain about 61% ketone, determined by oximation. 33 g. do not distil. They are saponified with 150 ml. of a solution of 15 g. KOH in methanol and in the presence of 10. ml. benzene. The neutral part is extracted with ether, washed with water, and distilled. 28.6 g. distil at 6468 C. under 0.1 mm. Hg; 114 0.9618; n =1.4985. Yield of the cyclization calculated on -dihydroionone: 64%. This yield may be increased by distilling faster or at a lower temperature, the product which has not reacted with the boric ester, for example,- by means of a continuous molecular distillation or by extraction. The yield then reaches Sulfuric acid may be replaced with advantage as proton-expanding substance by cation-exchange resins, such as described by Swistak, Hastagli and Zafiriadis (Comptes-rendus de lacademie des sciences, Paris, vol. 236, page 2325 (1953)). Other acids than sulfuric acid can also cflect the cyclization of 'y-dihydroionone.

In the following table are listed different acids together with their cyclization capacity at different concentrations and temperatures. In the last column is indicated the gay dihydroionone employed gm isolated alcohol of Formula III/IV/V Calculated according to. g mydrolonone Under the above reaction conditions the reaction product is not stable and undergoes dehydration and resinification. It is therefore important to continue the reaction and again distilled. Finally, the productis dissolved in as long as the yield is increasing and to stop it as soon ether, 'separated from a heavy brown layer of HBr, and as it falls. poured on a solution of CHsMgBr, made of 7.5 g. Mg and 30 g. CHsBr in 120 ml. ether. After boiling for 48 hours, EXAMPLE 3 the reaction product X is acidulated on ice, extracted with 5.75 Of v-dlhydroionone, dissolved in 30 of y ether and distilled. B. P. 12 mm. 105410; 3.24 g. This benzene, are treated with a current of 0.6 g. of BF3. The r i the dehydrogenated over (),6 Pd on h startmg temperature 18 The flask is cooled by coal at 260-280 during 20 hours. After extraction with a mixture of ice and salt; external temperature 3 C. ether, the product is distilled. 12 Hg In three minutes the temperature rises to +9.5 C. After 1 g Trinitmbenzoate p 153 1 55 Filtered on four addltlonal mmutes the temperature fans to O A1203, the latter gave the 1,2,4,6-tetramethyl-naphthalene At this moment the current of BF3 is stopped. Then X meltifig at 43440 C. Mixed melting points of the 52.32.?5i5lt12 t 2tt We a-1 NaOH and water, the reaction product is dried over nan? as.wen the Infrared Spectrum K2c03 and distilled. 5.25 g. distil under 0.15 mm. Hg shOWed immplete ldentlty a -Y -i at 67-70 C. These 5.25 g. are then heated with 14 g. ilaphthalene X prepared from P'methyl'acetophenonevvl B(OC2H5)3 to maximum 1 The alcohol and the in the following manner: VI 1s converted by a Reformatzky reaction, dehydration and saponification, to the B(OC2H5)3 in excess are distilled off. The distillation V is finally performed in vacuo at 0.5 mm. Hg up to 120 C. 361d Y an Arndt'Elstert reactlon, followed y Y The bori ester i a onified ith 15 1, f methanolig clization with H2804, this acid is successively converted to KOH (10%) in the presence of 2 ml. of benzene. The acid VIII and ketone IX, and finally by Grignard-reaction resulting reaction product is distilled. B. P. 0.12 mm. and dehydration to compound XI.

Hg at 72-73 C.; d4 =0.962; n =l.498. Yield 91%.

T e allophanates are prepared according to the general 25 Trinitrobenzoate C2uH19Os-Na-Calculated: C, 60.45%;

method described by Zobrist and Schinz in Helvetica H, Found; C, Chimica Acta. Vol. XXXV, page 2385 (1952). l53-l55.

CO l

cHi +ouionnrooon I 7 Elec D Remmatsky -nto c0011 +soolt/or-nNz Sapon. Arndt-Eistert COOH M. P. lee-132 c. n-=1.5122 VI VII VIII 1,1,6-trimethyl-6-hydroxy- ,2,3,5,6,7,8,9-octahydro- Grignard J naphthalene Pd EFT]; H10 HO G a g l g Semicarb. M. P. 184 0. M. P. 4344* 0.

IX X XI The pure isomers of Formulae III and respectively IV Compound VIII (C13H1aO2)--Calculated: C, 75.69%;

are difficult to obtain because of the mobility of their H, 8.80%. Found: C, 75.68%; H, 8.90%. double bond in the presence of acidic or alkaline re- Compound IX (C13H1sO)--Calculated: C, 82.93%; H, agents. The best way to separate them is the reduction 8.57%. Found: C, 82.87%; H, 8.75%.

of the dinitrobenzoates or the allophanates with a slight excess of LiA1 'I4 in tetrahydrofuran. Fractional distillation achievesithe purification- 14, 345 (1947)), durlng dehydration one methyl group of the 1,1-gem. dimethyl group of 1,1,6-trimethyl-6-hy- EXAMPLE 4 droxy-l,2,3,5,6,7,8,9-octahydronaphthalene shifts to the In Example 1, sulfuric acid may be replaced by ph position 2. The methyl group in position 4 shows clearly phoric acid which leads to substantially the same result that the Y -6 Y Y- l Y- as lf i acid. dronaphthalene has the double bond in 4,10 position.

To separate the mixture of the two isomers of For- In another Proof of Structures -d f y mulae III and IV from the isomer of Formula V, a fracheXahydfooctfllone'6 pf lia y U d Lardon, tional distillation under reduced pressure is best. The 29, 912 (1946) first treated Wlth methyl magne- Acc'ordin'g to E. Ledere'r' (Bull. Soc. chim. France (5) isomer of Formula V is" enriched in the higher boiling Slum iodide in a typical Gfi'gnal'd reaction The resulting fractions which partly crystallize. The crystallized part PI QU comprised a mixture f a substantial m t 0f is one of the two stereoisomeric compounds of Formula hydrocarbon and a Small q y of rt ary alcohol'ha'v- V a d melt t C, ing a melting point of 60 C. In this reaction no alcohol,

. 5 other than that shown in Formula V, page 2 of the specifi- Proof of Structure cation, could be formed. T he melting point of the com- The chemical constitution of 1:,1,6-trirnethyl-6-hydroxypound of Formula V plus the alcohol of the Grignard 1,2,3,5,6,7,8,9-octahydronaphthalene (Formula III) has synthesis showed that the products were identical as a been proved in the followingwayr mixed melting point identification. The lower boiling To 4.17 g. l,1,6-trimethyl-6-hydroxy-1,2,3,5,6,7,8,9-ocproducts are composed of the two other isomers as identitahydronaphthalene in 40 ml. CHCla is added at --10 C. fied by their infrared spectrum and their catalytic reduca solution of 3.44 g. Blz in 34 ml. CHCI3. After distillation. The tetrasubstituted double bond (Product IV) tion of the CHCls, the remaining'product is dissolved in 30 shows a band at l67Ocin. 1vvithout corresponding bendml. petroleum ether, then the solvent is removed by dising vibrations and is not reduced at ordinary pressure and tillation in vacuo, the product redissolved in 30 ml. ether, temperature in the presence of PtOzin ACOH. The trisubstituted double bond (Product III), which is not in the alpha beta position to the hydroxy group, shows a band at 1672 (stretching vibration) and at 830/796 (bending vibration) and is reduced under the named conditions. The fact that the products take up one oxygen to quantitatively produce an epoxide indicates the presence of a double bond in Products IV and III. Their formulas CrsI-lzzO must therefore be bicyclic. Moreover, the fact that this bicyclic alcohol is obtained by heating the dehydro-'y-ionone with an aqueous solution of phthalic acid, which usually gives no isomerization and therefore is a very mild reagent and which thereby cannot produce any other change in the carbon skeleton than that shown by Formula II, proves that the structure cannot be other than shown as Formula III and Formula IV. This reasoning is proved to be correct by the mere proven presence of the product of Formula V.

Further details of proof of structure, including infrared diagrams, are available in an article published by us in Helv. Chim. Acta, volume XXXIV, pages 183, 199 (195 6).

Quantitative composition of the obtained mixture (C13H2302) is formed, Which decomposes at 99 C. Yield 67-70%. The same iodohydrine is formed in 80% yield from pure wambrinol epoxide M. P. 57 C. Hence the original mixture contains 8l87% a-ambrinol. The remaining -14% are fi-ambrinol.

What is claimed is:

1. Compounds selected from the group consisting of 1,1,6 trimethyl 6 hydroxy 1,2,3,5,6,7,8,9 octahydronaphthalene having the formula CH3 CH:

r e c4, \14 om 2 9 7 l3 l -6| CH: C H n4 \5/ 0..

O CH:

1,1,6 trimethyl 6 hydroxy 1,2,3,4,5,6,7,8 octahydronaphthalene having the formula CH3 C 2 CH2 C C CHI that. M

and 1,1,6 trimethyl 6 hydroxy 1,2,3,4,6,7,8,9 octahydronaphthalene having the formula and mixtures thereof.

2. 1,1,6 trimethyl 6 hydroxy l,2,3,5,6,7,8,9-octahydronaphthalene having the formula CH3 CH3 3. 1,1,6 trimethyl 6 hydroxy 1,2,3,5,6,7,8,9 octahydronaphthalene having the formula CH CH3 4. A mixture of 1,1,6-trimethyl-6-hydroxy-1,2,3,5,6,7, 8,9-octahydronaphthalene having the formula CH CH2 and 1,1,6 trimethyl 6 hydroxy 1,2,3,4,6,7,8,9 octahydronaphthalene having the formula 5. A mixture of 1,1,G-trimethyl-6-hydroxy-1,2,3,5,6,7, 8,9-octahydronaphthalene having the formula 9 and 1,1,6 trimethyl 6 hydroxy 1,2,3,5,6,7,8,9 octahydronaphthalene having the formula 05a CH3 6. A process for preparing a mixture of tertiary alcohols comprising 1,1,6 trimethyl 6 hydroxy 1,2,3,5,6,7,8,9- octahydronaphthalene having the formula CH1 CH3 1,1,6 trimethyl 6 hydroxy 1,2,3,4,5,6,7,8 octahydronaphthalene having the formula CH; CH:

C CH:

in C(CHI 4 5 OH 042 C41 and 1,1,6 trimethyl 6 hydroxy 1,2,3,4,6,7,8,9 octahydronaphthalene having the formula 2 9 7 is '6 i/\\/ 6H: 8H

and mixtures thereof, comprising cyclizing a member of the group consisting of gamma dihydroionone, mixtures of gamma dihydroionone with at least one of its isomeric dihydroionones and acid hydrolizable keto derivatives of gamma dihydroionone.

7. The method as defined in claim 6, wherein the cyclization is effected with a cyclizing agent selected from the group consisting of dilute inorganic acids, dilute organic acids, and a dilute solution of boron fluoride.

8. The method as defined in claim 6, wherein the cycliz ation is effected with a cyclizing agent comprising boron fluoride.

9. The method as defined in claim 6, wherein the cyclization is effected with a cyclizing agent comprising dilute sulfuric acid.

10. The method as defined in claim 6, wherein the cyclization is eflj'ected with a cyclizing agent comprising phosphoric acid.

11. The method of forming 1,1,6-trimethyl-6-hydroxy- 1,2,3,5,6,7,8,9-octahydronaphthalene having the formula comprising cyclizing a member of the group consisting of gamma dihydroionone, mixtures of gamma dihydroionone with at least one of its isomeric dihydro-ionones and acid hydrolizable keto derivatives of gamma dihydroionone, and separating the 1,1,6-trimethyl-6-hydroxy-1,2,3,5,6,7, 8,9-octahydro-naphthalene from the mixture formed.

12. The method of forming 1,1,6-trimethyl-6-hydroxy- I 1,2,3,4,5,6,7,8-octahydronaphthalene having the formula comprising cyclizing a member of the group consisting of gamma dihydroionone, mixtures of gamma dihydroionone with at least one of its isomeric dihydroionones and acid hydrolizable keto derivatives of gamma dihydroionone, and separating the 1,1,6-trimethyl-6-hydroxy- 1,2,3,4,5,6,7,8-octahydro-naphtha1ene from the mixture formed.

13. The method as defined in claim 6, wherein the starting material is an acid hydrolizable keto derivative of gamma dihydroionone.

14. The method as defined in claim 6, wherein the starting material is a mixture of gamma dihydroionone with at least one other isomer of gamma dihydroionone.

15. The method as defined in claim 6, wherein the starting material is gamma dihydroionone.

No references cited. 

1. COMPOUNDS SELECTED FROM THE GROUP CONSISTING OF 1,1,6 - TREMETHYL 6 - HYDROXY - 1,2,3,5,6,7,8,9, - OCTAHYDRONAPHTHALENE HAVING THE FORMULA 